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Glycyrrhizin protects against porcine endotoxemia through modulation of systemic inflammatory response.

Wang W, Zhao F, Fang Y, Li X, Shen L, Cao T, Zhu H - Crit Care (2013)

Bottom Line: However, the effect of GL on HMGB1 expression in endotoxemia as well as its underlying molecular mechanism remained unclear.GL improved systemic hemodynamics and protected vital organs against porcine endotoxemia through modulation of the systemic inflammatory response.By reducing the serum level and gene expression of HMGB1 and other pro-inflammatory cytokines, GL may become a potential agent for the treatment of sepsis.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Glycyrrhizin (GL) was recently found to suppress high-mobility group box 1 (HMGB1)-induced injury by binding directly to it. However, the effect of GL on HMGB1 expression in endotoxemia as well as its underlying molecular mechanism remained unclear.

Methods: Twenty-one pigs were divided into four groups: sham group (n=3), control group (n=6), ethyl pyruvate group (n=6) and glycyrrhizin group (n=6). Pigs were anesthetized, mechanically ventilated, monitored and given a continuous intravenous infusion of lipopolysaccharide (LPS). Twelve hours after the start of the LPS infusion, ethyl pyruvate (30 mg/kg/hr) or glycyrrhizin (1 mg/kg/hr) was administered for 12 hours. Systemic and pulmonary hemodynamics, oxygen exchange, and metabolic status were measured. The concentrations of cytokines in serum and the corresponding gene and protein expressions in tissue samples from liver, lungs, kidneys, small intestine and lymph nodes were measured.

Results: GL maintained the stability of systemic hemodynamics and improved pulmonary oxygen exchange and metabolic status. GL also attenuated organ injury and decreased the serum levels of HMGB1 and other pro-inflammatory cytokines by inhibiting their gene and protein expression.

Conclusions: GL improved systemic hemodynamics and protected vital organs against porcine endotoxemia through modulation of the systemic inflammatory response. By reducing the serum level and gene expression of HMGB1 and other pro-inflammatory cytokines, GL may become a potential agent for the treatment of sepsis.

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Experimental design. After stabilization, LPS was infused to pigs for 24 hours and after 12 hours, the EP and GL groups were treated with the corresponding drug. Systemic and pulmonary hemodynamics, gas exchange and metabolic status were measured and blood samples collected at 6, 12, 18 and 24 hours. EP, ethyl pyruvate; GL, glycyrrhizin; LPS, lipopolysaccharide.
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Figure 1: Experimental design. After stabilization, LPS was infused to pigs for 24 hours and after 12 hours, the EP and GL groups were treated with the corresponding drug. Systemic and pulmonary hemodynamics, gas exchange and metabolic status were measured and blood samples collected at 6, 12, 18 and 24 hours. EP, ethyl pyruvate; GL, glycyrrhizin; LPS, lipopolysaccharide.

Mentions: All animals were allowed to stabilize for at least 60 minutes after surgery. After baseline data collection, the animals in the sham group were only anesthetized and infused with Ringer's solution, and the animals in the other three groups were given intravenous LPS (Escherichia coli 0111:B4, Sigma Chemical, St. Louis, Mo, USA, 20 mg/L in 5% dextrose) infusion and Ringer's solution for 24 hours. LPS was started at 1.7 μg/kg/hr until MPAP reached 35 mmHg in 2 hours; then the infusion rate was adjusted to maintain MPAP at 35 to 45 mmHg for the remaining 22 hours. If MAP decreased below 50 mmHg despite additional intravenous fluids, the LPS infusion was temporarily suspended. After 12 hours of continuous intravenous LPS infusion, the EP group received EP (Sigma Chemical) 30 mg/kg as loading dose over 10 minutes followed by 30 mg/kg/hr for 12 hours; the GL group received GL (Minophagen Pharmaceutical Co., Tokyo, Japan) 1 mg/kg as loading dose over 10 minutes followed by 1 mg/kg/hr for 12 hours (Figure 1). The additional intravenous fluid for the four groups was as follows: sham 6.95 ± 0.79, con 9.86 ± 1.28, EP 9.62 ± 0.55, and GL 9.07 ± 0.71 ml/kg/hr. Hydroxyethylstarch (HAES-Steril® 6% 200/0.5, Fresenius Kabi, Erlangen, Germany) was administered as required to maintain MAP > 60 mmHg, and 5% glucose solution was infused to keep arterial blood glucose levels between 5 to 7 mmol/L [1,26]. Con, EP and GL groups received similar amount of HAES (con, 64.0 ± 8.19, EP, 67.33 ± 6.66, and GL, 63.33 ± 4.93 ml).


Glycyrrhizin protects against porcine endotoxemia through modulation of systemic inflammatory response.

Wang W, Zhao F, Fang Y, Li X, Shen L, Cao T, Zhu H - Crit Care (2013)

Experimental design. After stabilization, LPS was infused to pigs for 24 hours and after 12 hours, the EP and GL groups were treated with the corresponding drug. Systemic and pulmonary hemodynamics, gas exchange and metabolic status were measured and blood samples collected at 6, 12, 18 and 24 hours. EP, ethyl pyruvate; GL, glycyrrhizin; LPS, lipopolysaccharide.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672474&req=5

Figure 1: Experimental design. After stabilization, LPS was infused to pigs for 24 hours and after 12 hours, the EP and GL groups were treated with the corresponding drug. Systemic and pulmonary hemodynamics, gas exchange and metabolic status were measured and blood samples collected at 6, 12, 18 and 24 hours. EP, ethyl pyruvate; GL, glycyrrhizin; LPS, lipopolysaccharide.
Mentions: All animals were allowed to stabilize for at least 60 minutes after surgery. After baseline data collection, the animals in the sham group were only anesthetized and infused with Ringer's solution, and the animals in the other three groups were given intravenous LPS (Escherichia coli 0111:B4, Sigma Chemical, St. Louis, Mo, USA, 20 mg/L in 5% dextrose) infusion and Ringer's solution for 24 hours. LPS was started at 1.7 μg/kg/hr until MPAP reached 35 mmHg in 2 hours; then the infusion rate was adjusted to maintain MPAP at 35 to 45 mmHg for the remaining 22 hours. If MAP decreased below 50 mmHg despite additional intravenous fluids, the LPS infusion was temporarily suspended. After 12 hours of continuous intravenous LPS infusion, the EP group received EP (Sigma Chemical) 30 mg/kg as loading dose over 10 minutes followed by 30 mg/kg/hr for 12 hours; the GL group received GL (Minophagen Pharmaceutical Co., Tokyo, Japan) 1 mg/kg as loading dose over 10 minutes followed by 1 mg/kg/hr for 12 hours (Figure 1). The additional intravenous fluid for the four groups was as follows: sham 6.95 ± 0.79, con 9.86 ± 1.28, EP 9.62 ± 0.55, and GL 9.07 ± 0.71 ml/kg/hr. Hydroxyethylstarch (HAES-Steril® 6% 200/0.5, Fresenius Kabi, Erlangen, Germany) was administered as required to maintain MAP > 60 mmHg, and 5% glucose solution was infused to keep arterial blood glucose levels between 5 to 7 mmol/L [1,26]. Con, EP and GL groups received similar amount of HAES (con, 64.0 ± 8.19, EP, 67.33 ± 6.66, and GL, 63.33 ± 4.93 ml).

Bottom Line: However, the effect of GL on HMGB1 expression in endotoxemia as well as its underlying molecular mechanism remained unclear.GL improved systemic hemodynamics and protected vital organs against porcine endotoxemia through modulation of the systemic inflammatory response.By reducing the serum level and gene expression of HMGB1 and other pro-inflammatory cytokines, GL may become a potential agent for the treatment of sepsis.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Glycyrrhizin (GL) was recently found to suppress high-mobility group box 1 (HMGB1)-induced injury by binding directly to it. However, the effect of GL on HMGB1 expression in endotoxemia as well as its underlying molecular mechanism remained unclear.

Methods: Twenty-one pigs were divided into four groups: sham group (n=3), control group (n=6), ethyl pyruvate group (n=6) and glycyrrhizin group (n=6). Pigs were anesthetized, mechanically ventilated, monitored and given a continuous intravenous infusion of lipopolysaccharide (LPS). Twelve hours after the start of the LPS infusion, ethyl pyruvate (30 mg/kg/hr) or glycyrrhizin (1 mg/kg/hr) was administered for 12 hours. Systemic and pulmonary hemodynamics, oxygen exchange, and metabolic status were measured. The concentrations of cytokines in serum and the corresponding gene and protein expressions in tissue samples from liver, lungs, kidneys, small intestine and lymph nodes were measured.

Results: GL maintained the stability of systemic hemodynamics and improved pulmonary oxygen exchange and metabolic status. GL also attenuated organ injury and decreased the serum levels of HMGB1 and other pro-inflammatory cytokines by inhibiting their gene and protein expression.

Conclusions: GL improved systemic hemodynamics and protected vital organs against porcine endotoxemia through modulation of the systemic inflammatory response. By reducing the serum level and gene expression of HMGB1 and other pro-inflammatory cytokines, GL may become a potential agent for the treatment of sepsis.

Show MeSH
Related in: MedlinePlus